tbuckley/cabot-search huggingface dataset:
Table of Contents
Authors: Ziad Massy, Tilman Drueke, Chao Zhang, Yun Xia, Frank Wagener, Nicole Van De Kar, Lambert Van Den Heuvel, Olivia Lenoir, Pierre-Louis Tharaux, Rajasree Menon, Andrew Bomback, Blue Lake, Christy Stutzke, Stephanie Grewenow, Steven Menez, Vivette D'agati, Sanjay Jain, Lorenzo Lodi, Maria Mastrolia, Federica Bello, Giovanni Rossi, Maria Angelotti, Yanick Crow, Paola Romagnani, Augusto Vaglio, David Bushinsky, Nancy Krieger, Wiebke Pirschel, Antonio Mestekemper, Bianka Wissuwa, Nadine Krieg, Sarah Kröller, Christoph Daniel, Florian Gunzer, Emanuela Tolosano, Michael Bauer, Kerstin Amann, Stefan Heinemann, Sina Coldewey, Anne Mühlig, Johanna Steingröver, Hannah Heidelbach, Madelaine Wingerath, Wiebke Sachs, Irm Hermans-Borgmeyer, Catherine Meyer-Schwesinger, Hoon Choi, Jin Lim, Christian Patry, Georg Hoffmann, Nicole Endlich, Katharina Bracke, Mariella Weiß, Andreas Guse, Moritz Lassé, Markus Rinschen, Fabian Braun, Tobias Huber, Victor Puelles, Claus Schmitt, Jun Oh, Lara Valiño-Rivas, Leticia Cuarental, Maria Ceballos, Arancha Pintor-Chocano, Maria Vanessa Perez-Gomez, Ana Sanz, Alberto Ortiz, Maria Dolores Sanchez-Niño, Lea Gerstner, Mengmeng Chen, Lina Kampf, Julian Milosavljevic, Konrad Lang, Ronen Schneider, Friedhelm Hildebrandt, Martin Helmstädter, Gerd Walz, Tobias Hermle, Søren Egstrand, Maria Lerche Mace, Marya Morevati, Anders Nordholm, Lars Engelholm, Skovhus Thomsen, Annemarie Brüel, Tally Naveh-Many, Yuliu Guo, Klaus Olgaard, Ewa Lewin, Jessica Van Der Weijden, Shekar Mahesh, Marco Van Londen, Stephan Bakker, Jan-Stephan Sanders, Gerjan Navis, Robert Pol, Joke Roodnat, Marcia Kho, Derya Yakar, Thomas Kwee, Ilja Nolte, Stefan Berger, Martin De Borst, Huda Al-Wahsh, Ngan Lam, Robert Quinn, Paul Ronksley, Manish Sood, Brenda Hemmelgarn, Navdeep Tangri, Thomas Ferguson, Marcello Tonelli, Pietro Ravani, Ping Liu, Simon Sawhney, Samira Bell, Corri Black, Christian Christiansen, Uffe Heide-Jørgensen, Simon Kok Jensen, Zhi Tan, Heather Walker, Matthew James Open, Xinyi Gao, Yueming Liu, Qiang He, Xiaogang Shen, Ryunosuke Noda, Wei Han, Yugo Shibagaki, Masahiko Yazawa, Kate Drummond, Matthew Davies, Ibrahim Batal, Heather Morris
Journal: Kidney International (2022)
Patterns of Testing for Tick-Borne Diseases and Implications for Surveillance in the Southeastern US
Authors: Amanda Brown Marusiak, Brandon D. Hollingsworth, Haley Abernathy, Aidin Alejo, Victor Arahirwa, Odai Mansour, Dana Giandomenico, John Schmitz, Carl Williams, Alexis M. Barbarin, Ross M. Boyce
Journal: JAMA Network Open (2022)

Tick-borne diseases (TBD), including spotted fever group rickettsiosis (SFGR), ehrlichiosis, and, increasingly, Lyme disease, represent a substantial public health concern throughout much of the southeastern United States. Yet, there is uncertainty about the epidemiology of these diseases because of pitfalls in existing diagnostic test methods.To examine patterns of diagnostic testing and incidence of TBD in a large, academic health care system.This cross-sectional study included diagnostic test results for TBD at UNC Health, a large academic health care system with inpatient and outpatient facilities, from January 1, 2017, to November 30, 2020. Participants included all individuals seeking routine care at UNC Health facilities who had testing for SFGR, ehrlichiosis, or Lyme disease performed during the study period.Rates of test positivity, testing completeness, and incidence of TBD.During the 4-year study period, 11 367 individuals (6633 [58.4%] female; 10 793 [95%] non-Hispanic individuals and 8850 [77.9%] White individuals; median [IQR] age, 53 [37-66] years) were tested for TBD. Among the 20 528 diagnostic tests performed, 47 laboratory-confirmed, incident cases of SFGR, 27 cases of ehrlichiosis, and 76 cases of Lyme were confirmed, representing incidence rates of 4.7%, 7.1%, and 0.7%, respectively. However, 3984 of SFGR tests (79.3%) and 3606 of Ehrlichia tests (74.3%) lacked a paired convalescent sample. Of 20 528 tests, there were 11 977 tests (58.3%) for Lyme disease from 10 208 individuals, 5448 tests (26.5%) for SFGR from 4520 individuals, and 3103 tests (15.1%) for ehrlichiosis from 2507 individuals. Most striking, testing for ehrlichiosis was performed in only 55% of patients in whom SFGR was ordered, suggesting that ehrlichiosis remains underrecognized. An estimated 187 incident cases of SFGR and 309 of ehrlichiosis were potentially unidentified because of incomplete testing.In this cross-sectional study, most of the patients suspected of having TBD did not have testing performed in accordance with established guidelines, which substantially limits understanding of TBD epidemiology. Furthermore, the data revealed a large discrepancy between the local burden of disease and the testing performed. These findings underscore the need to pursue more robust, active surveillance strategies to estimate the burden of TBD and distribution of causative pathogens.
Domain Expansion and Functional Diversification in Vertebrate Reproductive Proteins
Authors: Alberto M. Rivera, Damien B. Wilburn, Willie J. Swanson
Journal: Molecular Biology and Evolution (2022)

Abstract The rapid evolution of fertilization proteins has generated remarkable diversity in molecular structure and function. Glycoproteins of vertebrate egg coats contain multiple zona pellucida (ZP)-N domains (1–6 copies) that facilitate multiple reproductive functions, including species-specific sperm recognition. In this report, we integrate phylogenetics and machine learning to investigate how ZP-N domains diversify in structure and function. The most C-terminal ZP-N domain of each paralog is associated with another domain type (ZP-C), which together form a “ZP module.” All modular ZP-N domains are phylogenetically distinct from nonmodular or free ZP-N domains. Machine learning–based classification identifies eight residues that form a stabilizing network in modular ZP-N domains that is absent in free domains. Positive selection is identified in some free ZP-N domains. Our findings support that strong purifying selection has conserved an essential structural core in modular ZP-N domains, with the relaxation of this structural constraint allowing free N-terminal domains to functionally diversify.
Abstract B028: Overcoming resistance by driving melanoma cells into drug-susceptible states
Authors: Guillaume Harmange, Ben Emert, Dylan Schaff, Raul Reyes-Hueros, Sydney Shaffer
Journal: Cancer Research (2022)

Abstract The goal of this study is to target pre-existing heterogeneity in gene expression to ultimately overcome resistance to targeted therapy in melanoma. Despite significant advances in the treatment of melanoma, many patients still fail to achieve durable responses to therapy due to the development of drug resistance. Our lab recently discovered that in drug-naive melanoma rare cells transiently enter distinct gene expression states that allows them to ultimately survive treatment with targeted therapy (we refer to these cells as “primed for drug resistance”). The goal of this work is to develop a strategy to overcome this form of resistance by driving cells out of states primed for resistance and into drug-susceptible states. To identify the pathways that regulate the transition to the primed state we combined single-cell RNA sequencing with DNA barcoding to extract the transcriptional profiles and lineage information of over 7,000 drug-naive melanoma cells. We found that cells in lineages that transitioned into states primed for drug resistance express high levels of genes associated with TGFβ and PI3K signaling compared to lineages that stayed in a drug-susceptible state. To test whether TGFβ can directly cause cells to enter the primed state, we treated cells with recombinant TGFβ which led to a significant increase in the number of primed cells. Intriguingly, we also found that treating with TGFB receptor inhibitor or PI3K inhibitor reduced the number of cells in the primed cell state. Further, we sequentially treated these cells first with either the TGFB or PI3K inhibitor followed by targeted therapy and ultimately reduced the number of resistant colonies, demonstrating the potential for this therapeutic paradigm. To better understand how targeting the TGFB and PI3K pathways shift the population dynamics, we used single-cell RNA-seq and cellular barcoding to track lineages following treatment with TGFB, TGFB inhibitor, and PI3K inhibitor. Our analysis reveals the population changes following each therapy and directly demonstrates that treating with PI3K inhibitor decreases the number of primed cells, shifting the population into a drug-susceptible expression state. Ultimately, this work defines two key pathways underlying the primed cell state in melanoma and presents a therapeutic paradigm to eliminate this form of therapy resistance. Citation Format: Guillaume Harmange, Ben Emert, Dylan Schaff, Raul Reyes-Hueros, Sydney Shaffer. Overcoming resistance by driving melanoma cells into drug-susceptible states [abstract]. In: Proceedings of the AACR Special Conference on the Evolutionary Dynamics in Carcinogenesis and Response to Therapy; 2022 Mar 14-17. Philadelphia (PA): AACR; Cancer Res 2022;82(10 Suppl):Abstract nr B028.
Myeloid CCR2 Promotes Atherosclerosis after AKI
Authors: Anne M. Hüsing, Vera C. Wulfmeyer, Svenja Gaedcke, Susanne V. Fleig, Song Rong, David DeLuca, Hermann Haller, Roland Schmitt, Sibylle von Vietinghoff
Journal: Journal of the American Society of Nephrology (2022)

Significance Statement AKI impairs excretory function, but also leaves a damaged kidney. We demonstrate that a single episode of unilateral ischemia-reperfusion injury significantly promotes atherosclerotic plaque formation in mice. Renal inflammation preceded expression of myeloid and T cell genes in the atherosclerotic aorta. The chemokine receptor CCR2 was instrumental in inflammatory monocyte recruitment to the kidney, renal and aortic inflammatory macrophage marker CD11c expression, and enhanced aortic plaque formation after AKI. Delineating underlying mechanisms in atherosclerosis support the concept of a “toxic kidney” that promotes remote inflammation after ischemic reperfusion injury. Background The risk of cardiovascular events rises after AKI. Leukocytes promote atherosclerotic plaque growth and instability. We established a model of enhanced remote atherosclerosis after renal ischemia-reperfusion (IR) injury and investigated the underlying inflammatory mechanisms. Methods Atherosclerotic lesions and inflammation were investigated in native and bone marrow–transplanted LDL receptor–deficient ( LDLr−/− ) mice after unilateral renal IR injury using histology, flow cytometry, and gene expression analysis. Results Aortic root atherosclerotic lesions were significantly larger after renal IR injury than in controls. A gene expression screen revealed enrichment for chemokines and their cognate receptors in aortas of IR-injured mice in early atherosclerosis, and of T cell–associated genes in advanced disease. Confocal microscopy revealed increased aortic macrophage proximity to T cells. Differential aortic inflammatory gene regulation in IR-injured mice largely paralleled the pattern in the injured kidney. Single-cell analysis identified renal cell types that produced soluble mediators upregulated in the atherosclerotic aorta. The analysis revealed a marked early increase in Ccl2 , which CCR2 + myeloid cells mainly expressed. CCR2 mediated myeloid cell homing to the post-ischemic kidney in a cell-individual manner. Reconstitution with Ccr2−/− bone marrow dampened renal post-ischemic inflammation, reduced aortic Ccl2 and inflammatory macrophage marker CD11c, and abrogated excess aortic atherosclerotic plaque formation after renal IR. Conclusions Our data introduce an experimental model of remote proatherogenic effects of renal IR and delineate myeloid CCR2 signaling as a mechanistic requirement. Monocytes should be considered as mobile mediators when addressing systemic vascular sequelae of kidney injury.
The association between COVID-19 lockdowns and melanoma diagnosis and thickness: A multicenter retrospective study from Europe
Authors: Camila Scharf, Gabriella Brancaccio, Alessandro Di Stefani, Maria Concetta Fargnoli, Harald Kittler, Athanassios Kyrgidis, Aimilios Lallas, Caterina Longo, Josep Malvehy, Elvira Moscarella, Ketty Peris, Simonetta Piana, Susana. Puig, Luc Thomas, Giuseppe Argenziano
Journal: Journal of the American Academy of Dermatology (2022)
The PROMISE Minimal Risk Score Improves Risk Classification of Symptomatic Patients With Suspected CAD
Authors: Laust D. Rasmussen, Christopher B. Fordyce, Louise Nissen, C. Larry Hill, Brooke Alhanti, Udo Hoffmann, James Udelson, Morten Bøttcher, Pamela S. Douglas, Simon Winther
Journal: JACC. Cardiovascular imaging (2022)
Caught on film: NHS life during the pandemic
Journal: BMJ (2022)

Caught on film: NHS life during the pandemicSelfless, an exhibition of the work of photographer Jessica van der Weert that captures the working lives of NHS staff during the covid pandemic, has opened in Liverpool.The images-of staff across the health service in Northumberland and in Brent, London-offer a stark landscape of the UK at the height of the covid-19 crisis."I wanted to capture the enormous scale of loss, tragedy, and grief," said van der Weert."It's a vital moment in history that has to be captured, to ensure that future generations will remember, and that those who perished would never be forgotten."
Clinical assessment as a part of an early warning score—a Danish cluster-randomised, multicentre study of an individual early warning score
Authors: Pernille B Nielsen, Caroline S Langkjær, Martin Schultz, Anne Marie Kodal, Niels Egholm Pedersen, John Asger Petersen, Theis Lange, Michael Dan Arvig, Christian S Meyhoff, Morten H Bestle, Bibi Hølge-Hazelton, Gitte Bunkenborg, Anne Lippert, Ove Andersen, Lars Simon Rasmussen, Kasper Karmark Iversen
Journal: The Lancet Digital Health (2022)

BackgroundThe clinical benefit of Early Warning Scores (EWSs) is undocumented. Nursing staff's clinical assessment might improve the prediction of outcome and allow more efficient use of resources. We aimed to investigate whether the combination of clinical assessment and EWS would reduce the number of routine measurements without increasing mortality.MethodsWe did a cluster-randomised, crossover, non-inferiority study at eight hospitals in Denmark. Patients aged 18 years or older, admitted for more than 24 h were included. Admissions to paediatric or obstetric wards were excluded. The participating hospitals were randomly assigned 1:1 to start as either intervention or control with subsequent crossover. Primary outcomes were 30-day all-cause mortality (non-inferiority margin=0·5%) and average number of EWS per day per patient. The intervention was implementation of the Individual EWS (I-EWS), in which nursing staff can adjust the calculated score on the basis of their clinical assessment of the patient. I-EWS was compared with the National Early Warning Score (NEWS). The study is registered at ClinicalTrials.gov, NCT03690128 and is complete.FindingsUnique admissions longer than 24 h were included from Oct 15, 2018 to Sept 30, 2019. Of 90 964 patients assessed, n=46 470 were assigned to the I-EWS group and n=44 494 to the NEWS group. Mortality within 30 days was 4·6% for the I-EWS group, and 4·3% for the NEWS group (adjusted odds ratio 1·05 [95% CI 0·99–1·12], p=0·12). In subgroup analyses I-EWS showed increased 30-day mortality for hospitals that did I-EWS in fall–winter, which was probably due to seasonality, and within patients admitted in a surgical specialty. Overall risk difference was 0·22% (95% CI −0·04 to 0·48) meaning that the non-inferiority criteria were met. The average number of scorings per patient per day was reduced from 3·14 to 3·10 (ie, a relative reduction of 0·64% [95% CI −0·16 to −1·11], p=0·0084) in the I-EWS group.InterpretationIncluding clinical assessment in I-EWS was feasible and overall non-inferior to the widely implemented NEWS in terms of all-cause mortality at 30 days, and the number of routine measurements was minimally reduced. However I-EWS should be used with caution in surgical patients.FundingCapital Region Research Foundation, Gangsted Foundation, Candys Foundation, Herlev-Gentofte Hospital Research Foundation, Laerdal Foundation, and The Foundation of Director Boennelycke and wife.
Vaccination plus previous infection: protection during the omicron wave in Brazil
Authors: Thiago Cerqueira-Silva, Vinicius de Araujo Oliveira, Enny S Paixão, Pilar Tavares Veras Florentino, Gerson O Penna, Neil Pearce, Guilherme L Werneck, Maurício L Barreto, Viviane S Boaventura, Manoel Barral-Netto
Journal: The Lancet Infectious Diseases (2022)
Tislelizumab combined with chemotherapy as neoadjuvant therapy for surgically resectable esophageal cancer: A prospective, single-arm, phase II study (TD-NICE)
Authors: Xiaolong Yan, Hongtao Duan, Yunfeng Ni, Yongan Zhou, Xiaoping Wang, Haini Qi, Li Gong, Honggang Liu, Feng Tian, Qiang Lu, Jianyong Sun, Ende Yang, Daixing Zhong, Tao Wang, Lijun Huang, Jian Wang, None chaoyang Wang, Yuanyong Wang, Zhiyi Wan, Jie Lei, Jinbo Zhao, Tao Jiang
Journal: International Journal of Surgery (2022)
The potential role of N7-methylguanosine (m7G) in cancer
Authors: Yuejun Luo, Yuxin Yao, Peng Wu, Xiaohui Zi, Nan Sun, Jie He
Journal: Journal of Hematology & Oncology (2022)

Abstract N 7 -methylguanosine (m7G), one of the most prevalent RNA modifications, has recently attracted significant attention. The m7G modification actively participates in biological and pathological functions by affecting the metabolism of various RNA molecules, including messenger RNA, ribosomal RNA, microRNA, and transfer RNA. Increasing evidence indicates a critical role for m7G in human disease development, especially cancer, and aberrant m7G levels are closely associated with tumorigenesis and progression via regulation of the expression of multiple oncogenes and tumor suppressor genes. Currently, the underlying molecular mechanisms of m7G modification in cancer are not comprehensively understood. Here, we review the current knowledge regarding the potential function of m7G modifications in cancer and discuss future m7G-related diagnostic and therapeutic strategies.
Abstract B011: P300 histone acetyltransferase mediates glioma stem cell adaptive response to therapeutic stress
Authors: Sree Deepthi Muthukrishnan, Riki Kawaguchi, Pooja Nair, Alvaro Alvarado, Harley Kornblum
Journal: Cancer Research (2022)

Abstract Glioma stem-like and tumor cells exhibit phenotypic plasticity in response to environmental and therapeutic stress leading to tumor recurrence, but the underlying mechanisms remain largely unknown. In this study, we employed single-cell and whole transcriptomic analyses to uncover that radiation-stress induces a dynamic shift in functional states of glioma cells allowing for acquisition of vascular endothelial-like and pericyte-like cell phenotypes. These vascular-like cells provide trophic support to promote proliferation of tumor cells, and their selective depletion results in reduced tumor growth post-treatment in vivo. Mechanistically, the acquisition of vascular-like phenotype is driven by increased chromatin accessibility and H3K27 acetylation in specific vascular gene regions allowing for their increased expression post-treatment. Blocking P300 histone acetyltransferase activity using a small molecule inhibitor C646 or gene knockdown reverses the epigenetic changes induced by radiation, inhibits the adaptive conversion of GSC into vascular-like cells, reduces tumor growth and enhances animal survival. Our findings highlight an important role for P300 in mediating adaptive response of glioma stem cells to therapeutic-stress, and opens a new therapeutic avenue for preventing glioma recurrence. Citation Format: Sree Deepthi Muthukrishnan, Riki Kawaguchi, Pooja Nair, Alvaro Alvarado, Harley Kornblum. P300 histone acetyltransferase mediates glioma stem cell adaptive response to therapeutic stress [abstract]. In: Proceedings of the AACR Special Conference on the Evolutionary Dynamics in Carcinogenesis and Response to Therapy; 2022 Mar 14-17. Philadelphia (PA): AACR; Cancer Res 2022;82(10 Suppl):Abstract nr B011.
Hepatic p63 regulates glucose metabolism by repressing SIRT1
Authors: Maria J Gonzalez-Rellan, Eva Novoa, Natalia da Silva Lima, Amaia Rodriguez, Christelle Veyrat-Durebex, Samuel Seoane, Begoña Porteiro, Marcos F Fondevila, Uxia Fernandez, Marta Varela-Rey, Ana Senra, Cristina Iglesias, Adriana Escudero, Miguel Fidalgo, Diana Guallar, Roman Perez-Fernandez, Vincent Prevot, Markus Schwaninger, Miguel López, Carlos Dieguez, Roberto Coppari, Gema Frühbeck, Ruben Nogueiras
Journal: Gut (2022)

Objective p63 is a transcription factor within the p53 protein family that has key roles in development, differentiation and prevention of senescence, but its metabolic actions remain largely unknown. Herein, we investigated the physiological role of p63 in glucose metabolism. Design We used cell lines and mouse models to genetically manipulate p63 in hepatocytes. We also measured p63 in the liver of patients with obesity with or without type 2 diabetes (T2D). Results We show that hepatic p63 expression is reduced on fasting. Mice lacking the specific isoform TAp63 in the liver (p63LKO) display higher postprandial and pyruvate-induced glucose excursions. These mice have elevated SIRT1 levels, while SIRT1 knockdown in p63LKO mice normalises glycaemia. Overexpression of TAp63 in wild-type mice reduces postprandial, pyruvate-induced blood glucose and SIRT1 levels. Studies carried out in hepatocyte cell lines show that TAp63 regulates SIRT1 promoter by repressing its transcriptional activation. TAp63 also mediates the inhibitory effect of insulin on hepatic glucose production, as silencing TAp63 impairs insulin sensitivity. Finally, protein levels of TAp63 are reduced in obese persons with T2D and are negatively correlated with fasting glucose and homeostasis model assessment index. Conclusions. These results demonstrate that p63 physiologically regulates glucose homeostasis.
Haemostatic alterations and management of haemostasis in patients with cirrhosis
Authors: Ton Lisman, Stephen H. Caldwell, Nicolas M. Intagliata
Journal: Journal of Hepatology (2022)

Patients with cirrhosis frequently acquire complex changes in their haemostatic system including a decreased platelet count and decreased levels of various haemostatic proteins. Although historically patients with cirrhosis were thought to have a haemostasis-related bleeding tendency, it is now widely accepted that the haemostatic system of patients with cirrhosis remains in balance as a result of simultaneous changes in pro- and anti-haemostatic systems. The concept of rebalanced haemostasis has led to changes in clinical management, although firm evidence from well-designed clinical studies is largely lacking. For example, many invasive procedures in patients with cirrhosis and a prolonged prothrombin time are now performed without prophylaxis with fresh frozen plasma. Conversely, clinicians have become more aware of the need for anti-thrombotic therapy, even in those patients with abnormal routine coagulation tests. This paper will outline recent advances in pathogenesis, prevention and treatment of both bleeding and thrombotic complications in patients with cirrhosis. Among other topics, we will discuss the haemostatic status of acutely ill patients with cirrhosis, the various causes of bleeding in patients with cirrhosis, and how best to prevent or treat bleeding. In addition, we will discuss the hypercoagulable features of patients with cirrhosis, new insights into the pathogenesis of portal vein thrombosis, and how best to prevent or treat thromboses.